Oncostatin M Is a Biomarker of Diagnosis, Worse Disease Prognosis, and Therapeutic Nonresponse in Inflammatory Bowel Disease

Background: Oncostatin M (OSM) has been implicated in the pathogenesis of inflammatory bowel disease (IBD) and as a marker for nonresponsiveness to anti-tumor necrosis factor (TNF) therapy. We further unraveled the potential of OSM and related receptors as markers of diagnosis, prognosis, and therapy response in IBD. Methods: We collected inflamed mucosal biopsies and serum from patients with Crohn disease (CD) and with ulcerative colitis: (1) newly diagnosed patients who were treatment-naive, (2) patients initiating anti-TNF or (3) vedolizumab therapy, (4) postoperative patients with CD, and (5) multiple-affected families with IBD including unaffected first-degree relatives (FDRs). We measured the gene expression of mucosal OSM and its receptors OSMR/LIFR and co-receptor IL6SL and the protein expression of serum, OSM. Statistical significance was defined as P < 0.05. Results: Newly diagnosed patients showed significantly increased mucosal OSMIOSMR compared with control patients, with the highest enrichment for OSM (fold change [FC] >17.9). Likewise, ileal OSM/OSMR were significantly upregulated in postoperative recurrent CD. Serum OSM was increased in newly diagnosed patients and postoperative patients with recurrent CD (FC >= 2.6). In families with IBD, higher serum levels were observed in FDRs than in control families (FC = 2.2). Furthermore, elevated colonic OSMIOSMR (but not serum OSM) were associated with the early need for biologic therapy (FC >= 1.9), and higher OSM was also predictive of primary nonresponse to both anti-TNF and vedolizumab therapy (FC >= 2.4). Immunohistochemistry highlighted mucosal OSM expression in macrophages. Conclusions: We found that OSM is a diagnostic biomarker in the tissue and serum not only of newly diagnosed patients with IBD and postoperative patients with recurrent CD but also of their FDRs. Higher colonic OSM levels are furthermore associated with poor prognosis and with primary nonresponse to biologic therapies. Therefore, OSM could guide clinical decision-making.

Automated summary

The study found that Oncostatin M (OSM) can serve as a diagnostic biomarker in the tissue and serum of IBD patients, as well as predict prognosis and response to biologic therapies. Elevated ileal OSM/OSMR levels were significantly associated with postoperative recurrent CD. Serum OSM levels were increased in newly diagnosed patients and postoperative patients with recurrent CD. In families with IBD, higher serum levels were observed in first-degree relatives (FDRs) than in control families.